A trial of ponatinib for chronic myeloid leukaemia or Philadelphia positive acute lymphoblastic leukaemia (PACE)

Please note this trial is no longer recruiting patients.

This trial is looking at a drug called ponatinib for chronic myeloid leukaemia (CML) or acute lymphoblastic leukaemia (ALL) that is Philadelphia chromosome positive. It is for people whose leukaemia has got worse despite having other treatment.

Most people with CML have a change (mutation) to a gene which doctors describe as being Philadelphia positive. This affects a protein called BCR-ABL which signals to the body to make too many white blood cells. Some people with ALL also have this gene change in their leukaemia cells.

Certain drugs called tyrosine kinase inhibitors (TKIs) can block the BCR-ABL protein. But sometimes these drugs don’t work very well, or they stop working (the leukaemia becomes resistant to them).

In this trial, researchers are looking at a new TKI called ponatinib. The people taking part have already had a TKI called nilotinib or dasatinib, but their leukaemia has become resistant to it. Some people taking part have had a different TKI, but they have a gene mutation called T315I which means nilotinib or dasatinib are unlikely to help them.

The aim of this trial is to see if ponatinib helps people with CML or Philadelphia positive ALL who are resistant to other TKIs, cannot take them because of bad side effects, or who have the T315I gene mutation.

Please note – the trial has already recruited enough people with ALL so it is now only recruiting people who have accelerated phase CML with the T315I mutation.

Recruitment

Start 01/09/2010

End 30/09/2011

Phase

Phase 2

Who can enter

You can enter this trial if you

Have chronic myeloid leukaemia or Philadelphia positive acute lymphoblastic leukaemia
Have already had dasatinib or nilotinib and your leukaemia has become resistant, or you cannot take them because of bad side effects or you have had another TKI and have the T315I gene mutation
Are well enough to be up and about for at least half the day (performance status 0, 1 or 2)
Have satisfactory blood test results
Are willing to use a reliable form of contraception during the trial if there is any chance you or your partner could become pregnant
Are at least 18 years old

You cannot enter this trial if you

Have leukaemia that has spread to your brain or spinal cord, unless it has been successfully treated and you have had a negative lumbar puncture
Have had a very good response to treatment and your leukaemia is still in remission (there are different ways of measuring this and the trial doctors can explain this to you in more detail)
Have had another TKI in the last week or have not recovered from the side effects of earlier treatment (apart from hair loss) unless they are very mild
Have had major surgery in the last 2 weeks
Have CML in chronic phase or accelerated phase and are having hydroxyurea or a drug called anagrelide that you would continue to have in the 24 hours before the first dose of ponatinib, or you have had interferon, cytarabine or immunotherapy in the last 2 weeks, or any other chemotherapy, radiotherapy or experimental drug in the last 4 weeks
Have CML in blast phase and have had chemotherapy in the last 2 weeks (or any of the treatments listed in the point above)
Have ALL and are having steroids that you would continue to have in the 24 hours before the first dose of ponatinib, or have had vincristine in the last week, or any other chemotherapy in the last 2 weeks (or any of the treatments listed in the point for chronic and accelerated phase)
Have had a stem cell transplant in the last 60 days or have graft versus host disease
Need to carry on taking any medication that can affect the rhythm of your heart (the trial doctor can discuss this with you, but it is important that you don’t stop taking any medication without talking to your doctor first)
Need to carry on having any medication that damp down your immune system (immunosuppressants) apart from a short course of steroids
Have already had ponatinib
Have significant or active heart disease (the trial doctor can discuss this with you)
Have another bleeding disorder not related to your leukaemia
Have ever had inflammation of the pancreas (pancreatitis) or have abused alcohol
Have had another cancer in the last 3 years apart from non melanoma skin cancer, cervical carcinoma in situ, or prostate cancer that is controlled with treatment
Have an infection including HIV, hepatitis B or hepatitis C
Have any condition that could affect how you absorb tablets
Have any other medical condition that the trial doctors think could affect you taking part
Are pregnant or breastfeeding

Trial design

The trial will recruit about 350 people around the world. Everybody taking part in the trial will have ponatinib tablets once a day. You must take them at around the same time each day, about 2 hours after a light meal. You must not eat or drink anything apart from water for 2 hours after taking the tablets.

The trial team will give you a diary to record when you take the tablets. You take this diary to each hospital appointment.

You can carry on having treatment for up to 2 years.

Hospital visits

You will see the doctors and have some tests before you start treatment. The tests include

Physical examination
Blood tests
Heart trace (ECG)
Heart ultrasound (echocardiogram)
Bone marrow test

Every 4 week (28 day) period of treatment is called a treatment cycle. You go to see the trial team once a week during the 1st cycle of treatment, twice a month during the next 2 cycles and at least once a month after that. If you have ALL or CML in blast or accelerated phase, you go to hospital twice a month throughout the trial.

You will have blood tests at each visit and the trial team will ask how you are feeling and about any side effects you have had.

At the end of the 3rd cycle of treatment, you will have an ECG and an echocardiogram. And you have more bone marrow tests during the trial.

When you finish the treatment, you go back and see the trial team 2 weeks later. At this visit you have a physical examination, blood tests and an ECG and echocardiogram. You will have another appointment about a month later and then a member of the trial team will contact you every 3 months to see how you are for up to 2 years after you joined the trial.

Side effects

As ponatinib is a new drug, there may be some side effects we don’t know about yet. From earlier trials, doctors know the most common side effects can include

A drop in blood cells causing bleeding problems, tiredness and breathlessness
Inflammation of the pancreas (pancreatitis)
Feeling sick
Rash that may be red, itchy, bumpy or that looks like acne
Tiredness (fatigue)
Joint or muscle pain
Headache
Dry skin
Raised levels of triglycerides in your blood
Changes to the way your liver works that show in liver function tests

The trial doctors will talk to you about the possibility of any other side effects before you agree to join the trial.

You must not eat grapefruit or drink its juice with ponatinib, and you must stop taking herbal medicines such as St John’s Wort at least 2 weeks before starting ponatinib. This is because certain foods and drugs can affect the way ponatinib works.